Identification of Immunologic Mechanisms of Enhanced Ng Clearance Induced by Nm OMV-based Vaccines

Nm OMV 疫苗诱导 Ng 清除增强的免疫机制鉴定

• 批准号: 10362594
• 负责人: JOSEPH A DUNCAN
• 金额: $ 21.75万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-26 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362594
• 关键词: Animals; Antibiotic Resistance; Antibodies; Antibody Response; Antibody titer measurement; Antigen Presentation; Antigen Targeting; Antigens; Antimicrobial Resistance; B-Lymphocytes; Centers for Disease Control and Prevention (U.S.); Chlamydia trachomatis; Control Animal; Cuba; Data; Development Plans; Engineering; FDA approved; Female; Genital; Genitalia; Gonorrhea; Human; Immune; Immune Evasion; Immune response; Immunity; Immunization; Immunologics; Infection; Longitudinal observational study; Mass Vaccinations; Membrane; Mucous Membrane; Mus; Natural Immunity; Neisseria; Neisseria gonorrhoeae; Neisseria meningitidis; New Zealand; Norway; Outcome; Play; Recombinant Proteins; Research; Role; Serogroup B Neisseria meningitidis; Serum; Sexual Transmission; Specificity; Surface Antigens; T cell response; T-Lymphocyte; Testing; Time; Upper respiratory tract; Vaccinated; Vaccination; Vaccines; Vesicle; bactericide; base; clinical development; cross immunity; epidemiology study; gonorrhea vaccine; major outer membrane protein; mouse model; pathogen; pathogenic bacteria; preclinical development; prevent; reproductive tract; research clinical testing; response; stem; vaccine development; vaccine-induced immunity

Abstract Neisseria gonorrhoeae (Ng) is the most prevalent sexually transmitted bacterial pathogen globally, and gonococcal antibiotic resistance continues to rise. Potentially untreatable gonorrhea is recognized as an urgent threat by WHO and the US CDC. Gonococcal vaccine development is critical to help stem the spread of antimicrobial resistant Ng. Because naturally-acquired infection does not result in immunity from subsequent infection, immune responses required for protection from infection have never been definitively established for N. gonorrhoeae. Recently, a vaccine has been developed for N. meningitidis (Nm) serogroup B, and mass vaccination campaigns with this outer membrane vesicle (OMV)-containing vaccine have demonstrated collateral reduction in gonorrhea rates. Nm-OMV vaccines also show protection in a mouse model of genital Ng infection. For the first time,we have the opportunity to study both human and murine immune responses to effective vaccines, and identify likely correlates of protection. Project 1 in the Gonorrhea Vaccine Cooperative Research Center (GV CRC) will (1) determine whether murine humoral immune responses to Nm-OMV- containing vaccines are important in protection from Ng infection; (2) identify murine cellular immune mechanisms induced by Nm-OMV-containing vaccines that contribute to protection from Ng infection; and (3) determine humoral and cellular immune responses to Ng antigens induced by Nm-OMV-containing vaccine in humans. Defining immunologic mechanisms that provide protection from Ng infection is critical to advancing Ng vaccine development.!We will engage with all 4 scientific cores of the GV CRC. Our studies will set the stage for clinical evaluation of Nm-OMV vaccines for protection from Ng and will inform vaccine development plans in other GV CRC projects.

摘要 淋病奈瑟菌（Ng）是全球最流行的性传播细菌病原体， 淋球菌对抗生素的抗药性继续上升。潜在的无法治愈的淋病被认为是一个紧迫的 世界卫生组织和美国CDC的威胁。淋球菌疫苗的开发对于帮助阻止 抗微生物Ng.因为自然获得性感染不会导致免疫力从随后的 尽管免疫系统中存在感染，但保护免受感染所需的免疫应答从未明确建立， N.淋病最近，已经开发出了针对N.脑膜炎（Nm）血清群B和肿块 使用这种含有外膜囊泡（OMV）的疫苗的疫苗接种活动已经证明， 淋病发病率的间接降低。Nm-OMV疫苗也在生殖器感染的小鼠模型中显示出保护作用。 Ng感染。这是我们第一次有机会研究人类和小鼠对 有效的疫苗，并确定可能的保护相关性。淋病疫苗合作社项目1 研究中心（GV CRC）将（1）确定小鼠对Nm-OMV的体液免疫应答- 含有疫苗的疫苗在保护免受Ng感染方面是重要的;（2）鉴定小鼠细胞免疫 由含有Nm-OMV的疫苗诱导的有助于保护免受Ng感染的机制;以及（3） 确定由含Nm-OMV的疫苗诱导的对Ng抗原的体液和细胞免疫应答， 人类定义提供保护免受Ng感染的免疫机制对于促进Ng感染的发展至关重要。 疫苗研发！我们将与GV CRC的所有4个科学核心合作。我们的研究将为 Nm-OMV疫苗预防Ng的临床评价阶段，并将为疫苗开发提供信息 其他GV CRC项目的计划。